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Do white matter hyperintensities mediate the association between brain iron deposition and cognitive abilities in
M Valdés Hernández1,2, M Allerhand2, A Glatz1
1Department of Neuroimaging Sciences, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
Background And Purpose:
Several studies have reported associations between brain iron deposits (IDs), white matter hyperintensities (WMHs) and cognitive ability in older individuals. Whether the association between brain IDs and cognitive abilities in older people is mediated by or independent of total brain tissue damage represented by WMHs visible on structural magnetic resonance imaging (MRI) was examined.
Methods:
Data from 676 community-dwelling individuals from the Lothian Birth Cohort 1936, with Mini-Mental State Examination scores >24, who underwent detailed cognitive testing and multimodal brain MRI at mean age 72.7 years were analysed. Brain IDs were assessed automatically following manual editing. WMHs were assessed semi-automatically. Brain microbleeds were visually counted. Structural equation modelling was used to test for mediation.
Results:
Overall, 72.8% of the sample had IDs with a median total volume of 0.040 ml (i.e. 0.004% of the total brain volume). The total volume of IDs, significantly and negatively associated with general cognitive function (standardized β = -0.17, P < 0.01), was significantly and positively associated with WMH volume (std β = 0.13, P = 0.03). WMH volume had a significant negative association with general cognitive function, independent of IDs (std β = -0.13, P < 0.01). The association between cognition and IDs in the brain stem (and minimally the total brain iron load) was partially and significantly mediated by WMH volume (P = 0.03).
Conclusions:
The negative association between brain IDs and cognitive ability in the elderly is partially mediated by WMHs, with this mediation mainly arising from the iron deposition load in the brain stem. IDs might be an indicator of small vessel disease that predisposes to white matter damage, affecting the neuronal networks underlying higher cognitive functioning.
Insights
Brain iron deposits (IDs) are linked to cognitive decline in older adults, partly due to white matter hyperintensities (WMHs). This suggests IDs may indicate small vessel disease impacting brain function.
Area of Science:
- Neuroimaging
- Gerontology
- Neurology
Background:
- Associations between brain iron deposits (IDs), white matter hyperintensities (WMHs), and cognitive ability are reported in older individuals.
- The role of WMHs in mediating the relationship between brain IDs and cognitive function requires further investigation.
Purpose of the Study:
- To examine whether the association between brain IDs and cognitive abilities in older people is mediated by or independent of WMHs.
Main Methods:
- Utilized structural equation modeling on data from 676 community-dwelling older adults (Lothian Birth Cohort 1936).
- Assessed brain IDs, WMHs, and brain microbleeds using multimodal brain MRI.
- Included detailed cognitive testing and Mini-Mental State Examination scores.
Main Results:
- Brain IDs were negatively associated with general cognitive function (β = -0.17, P < 0.01) and positively associated with WMH volume (std β = 0.13, P = 0.03).
- WMH volume independently and negatively associated with general cognitive function (std β = -0.13, P < 0.01).
- WMH volume partially mediated the association between brain stem IDs and cognitive function (P = 0.03).
Conclusions:
- The negative association between brain IDs and cognitive ability in the elderly is partially mediated by WMHs, particularly those in the brain stem.
- Brain IDs may serve as an indicator of small vessel disease, contributing to white matter damage and cognitive impairment.
